This research proposal is designed to further characterize the factors which regulate cytoplasmic microtubule and microfilament assembly and distribution in normal and neoplastic cells. Recent findings in our laboratory and elsewhere indicate that transformation of cells in vitro is accompanied by specific alteration in the structure of the cytoskeleton as reflected in the assembly and distribution of cytoplasmic microtubules and microfilaments. The major objectives of this project will be to further characterize this phenomenon in terms of its extent and applicability to a variety of tumor cells in vitro and in vivo. Experiments will be designed to identify the biochemical and genetic factors which regulate cytoplasmic microtubule and microfilament assembly, disassembly, and distribution in cells. The association of microtubules and microfilaments with the plasma membrane and cell surface receptors will be investigated in normal and transformed cells. The elements of the cytoskeleton will be correlated with various properties of transformed cells such as altered cell surface properties, cell morphology, motility, growth potential in vitro, and of course, malignancy in several tumor models. Normal and transformed cell models will consist of established cell lines such as BALB/c 3T3, SV3T3, RAG, normal human PA2, Wl38, HeLa, CHO cells, and somatic cell hybrids derived from fusions of normal human x transformed mouse fibroblast. In addition, the study will include tumors of epithelial origin including murine mouse adenocarcinoma and rat hepatocellular carcinoma and their normal and premalignant counterparts.